The identification and treatment of hypercholesterolemic subjects has become a public health priority as a result of implementation of the National Cholesterol Education Program. Furthermore, there is increasing evidence that apolipoprotein levels can serve as important predictor of atherosclerotic disease. Apolipoprotein measurements aid in the diagnosis of dyslipoproteinemic states and help in monitoring the progress of dietary and drug intervention. Unfortunately, apolipoprotein measurements are being widely used without adequate standardization. Apolipoprotein measurements have not reached their full potential in the clinical laboratory because of problems in methodology, inadequate standardization, the lack of suitable common reference materials and the lack of reference methods. In turn, this has limited the ability to define adequate reference ranges for clinical use. The goals of this proposal are specifically designed to improve apolipoprotein standardization. The specific aims include: 1) develop reference immunoassays for apo A-I, and the Lp(a) lipoprotein; 2) maintain the candidate reference method apo B ELISA procedure and assist in its transferability to other laboratories; 3) evaluate the use of a primary apolipoprotein standards; 4) prepare and distribute reference serum pools to research clinical laboratories; 5) evaluate apolipoprotein reference materials from industry, governments or academia; and 6) evaluate the accuracy and precision of commercial apolipoprotein methods. Reference apolipoprotein procedures are needed for assigning target values to secondary reference pools and calibrators and for setting guidelines for acceptability of new methods. If improvements in apolipoprotein standardization are implemented, it will be possible to achieve accuracy in apolipoprotein measurements,k facilitate detection and treatment of dyslipoproteinemia, and identify subjects at risk for atherosclerotic cardiovascular disease.